The relation of glutathione to thyroid hormone metabolism was studied in cultured monkey hepatocarcinoma cells and normal rat hepatocytes. In carcinoma cells, the major deiodination of thyroxine affects the non-phenolic ring yielding reverse triiodothyronine whereas, in normal hepatocytes, it is phenolic ring deiodination yeilding triiodothyronine. By culturing cells in cystine- and/or methionine-deficient medium glutathione was reduced below 5 percent of control, but no decrease in deiodination was observed; therefore, the lesser variations observed in previous studies probably do not regulate deiodination. Transfer of sulfate to thyroid hormones and analogs was studied with monkey hepatocarcinoma cell extract and 2 homogeneous aryl sulfotransferases from rat liver. The differences in sulfation explain the relative sulfation of these compounds in vivo and in living cells. Metabolism of (3',5'-125I) and (3,5-125I) diiodothyronine and thyroxine in monkey hepatocarcinoma cells was studied. Various monodeiodination reactions were detected, but no diphenyl ether splitting was observed.